Rats with hippocampal damage are impaired on place learning in the water task when overtrained under constrained conditions

McDonald, Robert J.; Hong, Nancy S.

doi:10.1002/(sici)1098-1063(2000)10:2<153::aid-hipo4>3.0.co;2-a

Cited by 33 publications

(5 citation statements)

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“…Further, these same subjects were impaired at the spatial learning components of a navigation task but not the cued learning components. Taken together, this pattern of results suggests that maternal social isolation impacts learning and memory functions mediated by neural networks centered on the amygdala 40 , 37 and hippocampus 38 , 39 in offspring that lasts into adulthood.…”

Section: Discussionmentioning

confidence: 70%

Effects of maternal social isolation on adult rodent offspring cognition

McDonald,

Hong,

Trow

et al. 2023

Sci Rep

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Prenatal experiences can influence offspring physiology and behaviour through the lifespan. Various forms of prenatal stress impair adult learning and memory function and can lead to increased occurrence of anxiety and depression. Clinical work suggests that prenatal stress and maternal depression lead to similar outcomes in children and adolescents, however the long-term effects of maternal depression are less established, particularly in well controlled animal models. Social isolation is common in depressed individuals and during the recent COVID-19 pandemic. Accordingly, for this study we were interested in the effects of maternal stress induced via social isolation on adult offspring cognitive functions including spatial, stimulus–response, and emotional learning and memory that are mediated by different networks centered on the hippocampus, dorsal striatum, and amygdala, respectively. Tasks included a discriminative contextual fear conditioning task and cue-place water task. Pregnant dams in the social isolation group were single housed prior to and throughout gestation. Once offspring reached adulthood the male offspring were trained on a contextual fear conditioning task in which rats were trained to associate one of two contexts with an aversive stimulus and the opposing context remained neutral. Afterwards a cue-place water task was performed during which they were required to navigate to both a visible and invisible platform. Fear conditioning results revealed that the adult offspring of socially isolated mothers, but not controls, were impaired in associating a specific context with a fear-inducing stimulus as assessed by conditioned freezing and avoidance. Results from the water task indicate that adult offspring of mothers that were socially isolated showed place learning deficits but not stimulus-response habit learning on the same task. These cognitive impairments, in the offspring of socially isolated dams, occurred in the absence of maternal elevated stress hormone levels, anxiety, or altered mothering. Some evidence suggested that maternal blood-glucose levels were altered particularly during gestation. Our results provide further support for the idea that learning and memory networks, centered on the amygdala and hippocampus are particularly susceptible to the negative impacts of maternal social isolation and these effects can occur without elevated glucocorticoid levels associated with other forms of prenatal stress.

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Section: Discussionmentioning

confidence: 70%

Effects of maternal social isolation on adult rodent offspring cognition

McDonald,

Hong,

Trow

et al. 2023

Sci Rep

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“…These effects were particularly pronounced on the spatial probe trial and on spatial specificity measures. These results suggest that exercise improves hippocampal functions specifically as acquisition and retention of the spatial version of the water task has been consistently shown to be mediated by a network centered on the hippocampus [ 48 , 49 ].…”

Section: Resultsmentioning

confidence: 98%

Dramatic impacts on brain pathology, anxiety, and cognitive function in the knock-in APPNL-G-F mouse model of Alzheimer disease following long-term voluntary exercise

et al. 2022

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Background An active lifestyle is associated with improved cognitive functions in aged people and may prevent or slow down the progression of various neurodegenerative diseases including Alzheimer’s disease (AD). To investigate these protective effects, male APPNL-G-F mice were exposed to long-term voluntary exercise. Methods Three-month-old AD mice were housed in a cage supplemented with a running wheel for 9 months for long-term exercise. At the age of 12 months, behavioral tests were completed for all groups. After completing behavioral testing, their brains were assessed for amyloid pathology, microgliosis, and cholinergic cells. Results The results showed that APPNL-G-F mice allowed to voluntarily exercise showed an improvement in cognitive functions. Furthermore, long-term exercise also improved anxiety in APPNL-G-F mice as assessed by measuring thigmotaxis in the Morris water task. We also found reductions in amyloid load and microgliosis, and a preservation of cholinergic cells in the brain of APPNL-G-F mice allowed to exercise in their home cages. These profound reductions in brain pathology associated with AD are likely responsible for the observed improvement of learning and memory functions following extensive and regular exercise. Conclusion These findings suggest the potential of physical exercise to mitigate the cognitive deficits in AD.

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“…This idea emerged from a series of studies (Whishaw, Cassel, & Jarrard, ; Whishaw & Jarrard, ) showing that rats with damage to the hippocampus did show a “place response” invariants of the Morris water task (MWT), however, it is unclear whether animals used the relations among cues in the testing room as part of a spatial representation or some other combination of guidance and praxis information to compensate for a lack of true allocentric spatial knowledge of the escape platform location. The rats with hippocampal damage in these studies showed enduring impairments on many of the traditional measures of place navigation even when overtrained, under constrained training conditions (McDonald & Hong, ). We believe that although these experiments do show that rats with hippocampal damage can perform what appears to be a place response, the behavior is quantitatively and qualitatively different from that exhibited by normal rats on the standard place task.…”

Section: Discussionmentioning

confidence: 97%

“…We believe that although these experiments do show that rats with hippocampal damage can perform what appears to be a place response, the behavior is quantitatively and qualitatively different from that exhibited by normal rats on the standard place task. Previously, we have argued that, when an animal is trained on a spatial task, various representations could be acquired, stored and expressed via different neural systems that support some form of a place response (McDonald et al, ; McDonald & Hong, ; McDonald & White, ).…”

Section: Discussionmentioning

confidence: 99%

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Looking beyond the standard version of the Morris water task in the assessment of mouse models of cognitive deficits

et al. 2018

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Most studies investigating hippocampal-dependent learning and memory in mouse models of disease use the standard version of the Morris water task (MWT), in which a place is learned over several days. While useful in determining if there are learning and memory deficits, often it is not clear if memory acquisition, consolidation, or retrieval is affected. For rats, we developed a variant of the task in which we added a single-massed training session to a new location after the standard distributed version of the MWT. Using this version of the task, competition between these two spatial representations can then be assessed in a probe trial. We have found in rat models of Alzheimer's disease that this paradigm can detect subtle impairments that are often missed in the standard version of the MWT. To the best of our knowledge, MWT paradigm with a single-massed training session have never been used for mice. We sought to validate this paradigm for the use of assessing mouse models of disease. In the first two experiments, control mice did not have a preference for the new platform location, but instead with extensive training in the massed session displayed a preference for both the old and new locations. In the third experiment, a novel mouse model of Alzheimer's disease was impaired in the standard version of the MWT, but not in the massed training phase of this paradigm. Importantly, these data demonstrate that our paradigm is more informative in characterizing spatial learning and memory in mouse models of disease.

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Rats with hippocampal damage are impaired on place learning in the water task when overtrained under constrained conditions

Cited by 33 publications

References 29 publications

Effects of maternal social isolation on adult rodent offspring cognition

Effects of maternal social isolation on adult rodent offspring cognition

Dramatic impacts on brain pathology, anxiety, and cognitive function in the knock-in APPNL-G-F mouse model of Alzheimer disease following long-term voluntary exercise

Looking beyond the standard version of the Morris water task in the assessment of mouse models of cognitive deficits

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